UGN-101 offers durable RFS in low-grade upper tract urothelial carcinoma

Treatment with UGN-101 (Jelmyto) for pyelocalyceal solution led to a 3-year recurrence-free survival rate of 68% among patients with low-grade upper tract urothelial carcinoma (UTUC), according to findings from a long-term post commercialization study of the therapy published in Urologic Oncology: Seminars and Investigations.¹

UGN-101 was approved by the FDA in April 2020 based on data from the phase 3 OLYMPUS trial (NCT02793128), which showed favorable efficacy of the therapy in UTUC.

Solomon L. Woldu, MD

"The three-year durability data from this study further validate the potential of JELMYTO in providing long-term disease control for patients with low-grade upper tract urothelial cancer,” said lead author Solomon L. Woldu, MD, an assistant professor of urology at UT Southwestern Medical Center in Dallas, Texas, in a news release on the findings.² “Notably, we found that recurrence-free survival was not influenced by factors like tumor size or location, highlighting the broad applicability of this treatment. The potential benefits of maintenance therapy are encouraging, and further research will be key in confirming its role in improving outcomes for these patients.”

In total, the study included 56 patients with UTUC who had no evidence of disease following UGN-101 induction. Patients were enrolled across 15 academic and community centers. The median age of participants was 73 years (SD, 9.8). The majority of patients (93%) had low-grade disease.

With a median follow-up of 23.5 months, 21.4% of patients experienced a recurrence. At 3 years, the RFS rate was 68% among those with low-grade UTUC. The median time to recurrence was not reached, but the mean survival was estimated to be 29.0 months (95% CI, 26-32 months).

RFS was significantly worsened in patients with high grade disease vs those with low grade disease (P = .04). Overall, 50% (2 of 4) of patients with high grade disease experienced a recurrence following an initial response to treatment.

Among all patients, 27% (15 of 55) received maintenance therapy. The risk of recurrence was significantly improved among those who received maintenance therapy vs those who did not (P = .021). In total, 1 patient who received maintenance therapy experienced recurrence, whereas approximately half of the patients who did not receive maintenance therapy experienced a recurrence within 2 years.

The estimated mean survival was 34.3 months (95% CI, 32.4-36.1 months) among those who received maintenance therapy vs 24.6 months (95% CI, 21.2-27.9 months) among those who did not (P = .02).

However, the authors caution, “The administration of maintenance treatment did appear to be associated with significantly better RFS, however, it should be acknowledged that only 15 patients received maintenance therapy and we feel that further study or potentially even a prospective trial on this subject is required to determine the value of maintenance treatments.”

Additional findings showed no difference in the risk of recurrence between those who received UGN-101 in the adjuvant setting vs those who received it in the chemoablative setting. Further, no differences were observed based on tumor size prior to UGN-101 induction, multifocality, tumor location, or UGN-101 induction technique.

According to the authors, these data complement findings from the phase 3 OLYMPUS trial, which demonstrated that 56% of patients remained in complete response at a median follow-up of 11.8 months. While these real-world findings contribute much longer-term follow-up, the patients from the current analysis differ from those enrolled in the phase 3 trial in that patients were able to receive treatment in the adjuvant setting and were eligible for enrollment if they had ureteral involvement. The study also allowed a small number of patients with high-grade disease.

Thus, the authors write, “Further study is needed to understand longer term outcomes and potential late adverse events, and also to more clearly define the role of maintenance UGN-101.”

To that end, a prospective registry is currently ongoing to obtain longitudinal real-world usage data in patients with UTUC. As of July 2024, the JELMYTO uTRACT Registry (NCT05874921) had enrolled 191 participants across 19 clinical sites, with a total enrollment goal of 400 patients.^3,4

References

1. Woldu SL, Igel D, Johnson B, et al. Durability of response of UGN-101: Longitudinal follow up of multicenter study. Urol Oncol. 2025 20:S1078-1439(24)01059-7. doi:10.1016/j.urolonc.2024.12.279

2. New real-world durability of response data for JELMYTO reports 68% recurrence-free survival rate (RFS) at three years across a broad patient population with low-grade upper tract urothelial cancer (LG-UTUC). News release. UroGen Pharma. Published online and accessed January 22, 2025. https://investors.urogen.com/news-releases/news-release-details/new-real-world-durability-response-data-jelmyto-reports-68

3. New data from a long-term follow-up study to the OLYMPUS trial show median duration of response of four years in patients who achieved a complete response with JELMYTO. News release. UroGen. November 26, 2024. Accessed January 22, 2025. https://investors.urogen.com/news-releases/news-release-details/new-data-long-term-follow-study-olympus-trial-show-median

4. uTRACT Jelmyto Registry: A registry of patients with upper tract urothelial cancer (UTUC) treated with Jelmyto (uTRACT). ClinicalTrials.gov. Last updated December 5, 2023. Accessed January 22, 2025. https://clinicaltrials.gov/study/NCT05874921